The present invention relates to a method for synthesizing C-glycosides of ulosonic acids, as well as intermediates thereof and particular C-glycosides prepared by the method.
Ulosonic acids are a diverse family of complex monosaccharides that serve important biological functions. The most common ulosonic acids are N-acetylneuraminic acid (NANA), 3-deoxy-D-glycero-D-galactonulosonic acid (KDN) and 3-deoxy-D-manno-2-octulosonic acid (KDO), important constituents of many glycoconjugates, often occupying the non-reducing ends of oligosaccharide chains. Glycoproteins containing NANA, for example, are involved in a number of biological processes including cell interactions with other cells, microorganisms, toxins and antibodies.1 The biologic functions of ulosonic acids are derived from their size, negative charge and their natural position as the terminal residue on cell surface glycoconjugates. C-glycosides of ulosonic acids are of particular interest for their potential pharmaceutical applications. These are expected to have both improved enzymatic hydrolytic stability and exoanomeric conformation similarity to the corresponding O-glycosides.2 
The synthesis of C-glycosides is a well established area of carbohydrate chemistry.3 The utility of glycosyl chlorides in the formation of C-glycosides has been appreciated for some time. Until recently the aglycone portion of this radical pathway was limited to allylsilane, 1,3-dimethoxy benzene.3a Sinaÿ4 and Wong5 examined the possibility of coupling chloride and ketone (or aldehyde) under SmI2 mediated radical reactions. In the presence of a protecting group at C-2, glycal was produced, in place of the desired C-glycoside. NANA-C-glycoside was reported by Bednarski6 through NANA-glycosyl chloride with (nBu)3SnCH2CHxe2x95x90CH2 and catalytic amount of [(nBu)3Sn]2, affording 1:1 mixture of NANA-C-glycoside. By using glycosyl aryl sulfones, Beau and co-workers prepared the corresponding 1,2-trans-C-glycosides under Barbier conditions.7 A similar approach was used in the first examples of the NANA8 and KDN9 C-disaccharide synthesis in our laboratory, using pyridyl and phenyl sulfones as nucleophiles. There are two disadvantages of using sulfones as nucleophiles: 1) additional steps are required for their preparation and 2) they often produce a very unpleasant odor.
Accordingly, an object of the present invention is to provide a method for synthesizing C-glycosides of ulosonic acids such as Neu5Ac, by which diastereocontrolled synthesis of xcex1-C-glycosides of ulosonic acids is attained, which is simpler than the known method and free from the unpleasant odor caused by the use of a sulfone derivative.
The present inventors intensively studied to discover that the above-mentioned object may be attained by reacting a halogenated ulosonic acid with an aldehyde or ketone compound in the presence of a lanthanide metal halide, thereby completing the present invention.
That is, the present invention provides a method for synthesizing C-glycosides of ulosonic acids comprising the step of reacting a halogenated ulosonic acid with an aldehyde or ketone compound in the presence of a lanthanide metal halide, such as samarium iodide.
By the present invention, a method for synthesizing C-glycosides of ulosonic acids, by which diastereocontrolled synthesis of xcex1-C-glycosides of ulosonic acids is attained, which is simpler than the known method and free from the unpleasant odor caused by the use of a sulfone derivative, was provided.